2GSG

Crystal structure of the Fv fragment of a monoclonal antibody specific for poly-glutamine

Summary for 2GSG

• Entry DOI: 10.2210/pdb2gsg/pdb
• Descriptor: monoclonal antibody light chain, monoclonal antibody heavy chain, SULFATE ION, ... (4 entities in total)
• Functional Keywords: fv, monoclonal antibody, poly-glutamine, immune system
• Biological source: Mus musculus (house mouse); More
• Total number of polymer chains: 4
• Total formula weight: 51949.85

Authors

Li, P.,Huey-Tubman, K.E.,West Jr., A.P.,Bennett, M.J.,Bjorkman, P.J. (deposition date: 2006-04-26, release date: 2007-04-24, Last modification date: 2024-10-30)

Primary citation

Li, P.,Huey-Tubman, K.E.,Gao, T.,Li, X.,West Jr., A.P.,Bennett, M.J.,Bjorkman, P.J.
The structure of a polyQ-anti-polyQ complex reveals binding according to a linear lattice model.
Nat.Struct.Mol.Biol., 14:381-387, 2007

PubMed Abstract: Huntington and related neurological diseases result from expansion of a polyglutamine (polyQ) tract. The linear lattice model for the structure and binding properties of polyQ proposes that both expanded and normal polyQ tracts in the preaggregation state are random-coil structures but that an expanded polyQ repeat contains a larger number of epitopes recognized by antibodies or other proteins. The crystal structure of polyQ bound to MW1, an antibody against polyQ, reveals that polyQ adopts an extended, coil-like structure. Consistent with the linear lattice model, multimeric MW1 Fvs bind more tightly to longer than to shorter polyQ tracts and, compared with monomeric Fv, bind expanded polyQ repeats with higher apparent affinities. These results suggest a mechanism for the toxicity of expanded polyQ and a strategy to link anti-polyQ compounds to create high-avidity therapeutics.

PubMed: 17450152
DOI: 10.1038/nsmb1234

Experimental method

X-RAY DIFFRACTION (2.1 Å)